%0 Journal Article
%A Jin, Chunmei
%A Emam, Mahmoud
%A Klauck, Sabine M
%A Ali, Nadeen T
%A Salem, Rofaida
%A Eldehna, Wagdy M
%A Efferth, Thomas
%A Hegazy, Mohamed-Elamir F
%A Dawood, Mona
%T Targeting sensitive and multidrug resistant leukemia cells with a novel benzofuran-isatin conjugate.
%J European journal of pharmacology
%V 997
%@ 0014-2999
%C New York, NY [u.a.]
%I Elsevier
%M DKFZ-2025-00612
%P 177538
%D 2025
%Z 2025 Mar 22:997:177538
%X Benzofuran-isatin conjugates are considered as promising compounds in cancer prevention and treatment. However, it is not known yet whether these compounds are useful to effectively treat multidrug-resistant tumors. In this study, we investigated the activity of G-5e, a novel benzofuran-isatin conjugate in a panel of cell lines exhibiting well-known drug resistance mechanisms (P-gp, BCRP, TP53, EGFR). P-glycoprotein overexpressing CEM/ADR5000 cell line displayed notable hypersensitivity (collateral sensitivity) to G-5e, which was mediated through autophagic cell death activation including downregulation of the autophagy suppressor RND2, upregulation of the autophagy inducer LC3B, and G0/G1 phase arrest during cell cycle progression. Independent of collateral sensitivity, transcriptomic analyses also revealed that G-5e caused downregulation of NF-κB and ERK1/2 pathways. Our findings highlight the potential of benzofuran-isatin conjugates to combat multidrug resistance and the role of RND2 for collateral sensitivity.
%K Autophagic cell death (Other)
%K Benzofuran-isatin conjugate (Other)
%K Collateral sensitivity (Other)
%K Multidrug resistance (Other)
%K P-glycoprotein (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40122501
%R 10.1016/j.ejphar.2025.177538
%U https://inrepo02.dkfz.de/record/300114